1. Field of the Invention
This invention relates generally to image processing and, more specifically, to automated digital image processors useful for the identification of dividing cells for the examination of various biological cellular events.
2. Prior Art
Much of the experimental work in the field of cell and molecular biology of cultured cells involves the assay of the proliferative activity of these cells. This is especially true for problems in biological time, rhythmicity and time sense which require for their resolution continuous surveillance and frequent data acquisition.
Critical to such work is an accurate count of incidents of mitosis, or cell division, in a cell culture. Incidents of mitosis are easily identified because mitotic cells in culture tend to round up and become refractile and annular in appearance under phase contrast illumination. Thus it is possible for a human observer to count incidents of mitosis by observing the cell culture under such illumination.
Up to the present time, all of this information has been collected by researchers by hand without the extensive use of computers. This is a particular problem because the need for extensive observation of the growth of cells in such cultures makes human observation an inconveniently long and tedious process in a laboratory setting. In addition, such observation requires a high degree of accuracy, and consequently several observers must be used to insure such accuracy.
One present method for performing such experiments is to place a plated culture of cells under a microscope under phase contrast illumination, and to record the microscopic images over time using a video tape recorder having time lapse videophotography capability. The time at which each cell divided, or more typically, elapsed time from a predetermined event can be determined from the videotapes. This information has been provided by a digital clock which generates a time signal that is superimposed on the viewing video screen. Thus, the number of cells dividing during the experiment, and the time at which each division occured can be obtained. A 48:1 time compression is generally used so that a 48 hour recorded observation can be viewed in one hour. Of course, since multiple events may occur on the screen at the same time, an observer may be required to review the tape a multiple number of times to observe all mitotic events. Thus, the review of a 48 hour tape may easily take eight hours or longer for a skilled human observer to complete.
What is required is an automated means for recording these incidents of mitosis which is rapid, automated, and non-perturbing. This last criteria is particularly important in research involving rhythmicity and time sense. As disclosed below, the present invention provides such a means. Such an automated system permits continual observation of cell cultures over extended periods of time that was not available under the manual methods of the prior art. The use of such automated system would make such data handling and analysis faster and significantly more accurate, and further would enable the researchers to derive additional information from such experiments which have heretofore been very difficult to obtain on a large population of cells, because of the difficulty in tracking individual cells and their progeny on a large scale.